By Michael Smith, North American Correspondent, MedPage Today
Published: September 13, 2010

Action Points

* Note that the drug appears to be effective and safe in patients with multidrug-resistant TB, defined as a strain resistant to the first-line drugs isoniazid (Nydrazid) and rifampin (Rifadin).

* Point out that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

BOSTON -- Patients with multidrug-resistant TB (MDR-TB) given a new anti-TB drug -- TMC207 -- combined with a background regimen, responded almost twice as fast as those on placebo with the background regimen, a researcher reported here.

Final results from the first part of a stage IIb trial among 47 patients, found the median time to culture conversion was 11 weeks for those treated for eight weeks with TMC207 and the five-drug MBR-TB background regimen, according to Andreas Diacon, MD, of the University of Stellenbosch in South Africa.

In contrast, the median time for patients assigned to placebo combined with the five-drug background regimen was 18 weeks, Diacon reported here at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

"Importantly," Diacon said, "these patients were only treated with TMC207 for eight weeks and still there is a significant reduction in the median time to culture conversion compared with placebo."

The drug has been closely followed (See ICAAC-IDSA: Novel Drug Shows Power in MDR-TB) but Diacon presented the final results of the first stage of the trial, which involved eight weeks of therapy with TMC207 and two years of the background regimen alone.

A second stage of the trial, with a different and larger cohort of patients treated for 24 weeks, is currently under way, he added.

TMC207 interferes with synthesis of adenosine triphosphate in Mycobacterium tuberculosis cells, but not in other cells, even those of closely related bacteria. Inhibiting the compound reduces the energy available for the TB bacteria to combat other drugs or to reproduce.

The researchers were looking at the safety and tolerability of the drug, as well as efficacy, in 47 patients with multidrug-resistant TB, defined as a strain resistant to the first-line drugs isoniazid (Nydrazid) and rifampin (Rifadin).

They were treated with a five-drug background regimen, which varied from patient to patient but usually included ethionamide (Trecator), pyrazinamide, kanamycin (Kantrex), and ofloxacin (Floxin). TMC207 was given daily at 400 milligrams for two weeks, followed by 200 milligrams three times weekly for six weeks.

At the end of the first stage of the trial, Diacon said, 81% of those treated with TMC207 were considered cured, defined as two consecutive negative cultures at least 28 days apart and no recurrence of the disease.

In contrast, 57% of those getting the background regimen alone were considered cured, a difference that was significant at P=0.03, he said.

The drug was generally well tolerated, Diacon said. No patients stopped the drug because of adverse events, and the proportions of patients with grade 3 and 4 adverse events were similar between the arms -- 26% for TMC207 and 21% for placebo.

The results are exciting, according to Patrick Charles, MD, PhD, of Austin Health in Heidelberg, Australia, who moderated the session at which the study was presented but who was not involved in the research.

"It's really the first new drug to treat these extremely resistant cases," he told MedPage Today.

For patients with multidrug-resistant TB, he said, treatment options are "very limited and very expensive, so to have a new drug is very exciting."

According to the abstract, preliminary results from the second stage of this trial, involving 161 MDR-TB patients with TMC207 administered for six months, are expected soon.

The study was supported by Tibotec. Diacon said he had no disclosures. Several other authors are employees of the company.